The Sleep Research Society Digital Dissertation library highlights postdoctoral research conducted by SRS members at a postdoctoral or graduate student level. Research professionals of all levels of experience may browse dissertations on sleep, sleep disorders, circadian rhythms and sleep & behavior.

The SRS encourages all young investigators to participate and showcase their work. To submit a dissertation for display or to edit an existing dissertation use the Add/Edit Dissertation online tool.

Roles of the circadian and reward systems in alcoholism

Author:Allison Brager, PhDUniversity/Institution:
Kent State University
Date Accepted:
8/11/2011
Area of Study:Circadian RhythmsAbstract:
This dissertation addresses primary mechanisms for alcoholism through the assessment of ethanol disruption to the mammalian circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The mouse strain utilized (C57BL/6J) demonstrated moderate ethanol intake (~12 g/kg/day), preference (50%), and relapse risk. Chronic ethanol intake, its withdrawal, and subsequent re-introduction had adverse effects on photic entrainment and the circadian distribution of locomotor activity. An acute, systemic ethanol challenge and chronic ethanol intake dose-dependently attenuated light-induced phase-delays of behavioral circadian rhythms. In vivo microdialysis administration of ethanol (500 mM) in the SCN revealed that it is a direct site of ethanol disruption to photic entrainment processes. An ethanol challenge at midday attenuated 8-OH-DPAT-induced phase-advances, while chronic ethanol intake and an intra-SCN microdialysis perfusion had no effect on this response. A nonfunctional homolog of the clock gene, PER2, in wild-type mice elevated ethanol intake and preference, owing, in part, to an additional circadian phase of ethanol intake. Ethanol intake and preference associated with PER2 mutation were rescued to wild-type levels through a systemic administration of acamprosate or constant-release acamprosate microimplants in circadian and reward areas. Brain mapping with acamprosate microimplants also identified circadian (SCN, intergeniculate leaflet) and reward (ventral tegmental, accumbal, and penducular areas) sensitive to the suppressive effects of acamprosate, though the extent of suppression was significantly less in PER2-mutant vs. wild-type mice. These results suggest that the disruptive effects of ethanol binging and chronic use on circadian entrainment can facilitate a downward spiral of alcohol dependence and chronobiological disturbances.

The Role of Intercellular Communication in Synchronization and Maintenance of Rhythms in the Mammalian Circadian Clock

Author:Sara J Aton, PhDUniversity/Institution:
Washington University
Date Accepted:
8/17/2006
Area of Study:Circadian RhythmsAbstract:
Daily rhythms in mammalian behavior and physiology are mediated by a circadian (near-24-hour) pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus. Individual SCN neurons fire rhythmically with circadian periodicity, and maintain circadian rhythms in “clock gene” expression. Previous studies have emphasized the mechanisms for intracellular generation of circadian rhythms. However, the roles played by intercellular communication in maintaining neuronal rhythms and synchronizing them to one another in vivo are not well understood. We utilized multielectrode array and low-light imaging technologies to make long-term in vitro recordings of firing rate and Period::luciferase rhythms from individual SCN neurons and SCN ensembles. In combination with these techniques, we manipulated cell density and modified the ratio of neurons with wild-type or shortened period to test the role of intercellular signaling in maintaining neuronal rhythmicity, and the precision, periodicity, and synchrony of rhythms across the SCN network. We find that SCN neurons influence one another’s periodicity through intercellular signaling, and that density-dependent signals regulate the synchrony and precision, and rhythmicity of individual SCN neurons.
We also tested the necessity of three candidate signals - ??aminobutryric acid (GABA), vasoactive intestinal polypeptide (VIP), and Gi/o signaling – for SCN rhythmicity and synchrony. Antagonism of endogenous GABA increased daily peak firing rates, but did not impair neuronal rhythmicity or synchrony. In contrast, SCN neurons from mice lacking VIP or its cognate receptor VPAC2 show disrupted synchrony and a reduction in the proportion of neurons with daily rhythms in firing. Antagonism of Gi/o similarly impaired rhythmicity and synchrony among SCN neurons. Our results establish VPAC2 signaling and activation of Gi/o, as necessary signals for rhythms and synchrony in the SCN, and rule out GABA as a necessary mediator of these processes. Critically, VPAC2 is not functionally coupled to Gi/o in SCN neurons, but acts in opposition to Gi/o at downstream targets, such as adenylyl cyclase. Thus these data support a model in which both activation and inhibition of adenylyl cyclase must be temporally regulated to mediate rhythmicity and synchrony in subpopulations of neurons within the SCN.

Diurnal Rhythms in Co-Sleeping Couples: Does Being “In Sync” Matter?

Author:Brant P Hasler, PhDUniversity/Institution:
University of Arizona
Date Accepted:
4/15/2008
Area of Study:Circadian Rhythms, Sleep & BehaviorAbstract:
Subjective feeling, or mood, is not just a product of situational and dispositional
factors, but is also based in part on underlying circadian rhythms. Notably, accumulating evidence suggests that circadian patterning is limited to positive affect, possibly as an adaptive manifestation of an appetitive motivational system. Furthermore, dispositional factors may influence the observed patterning, such as blunting the rhythm in positive affect when depression is present. The present study sought to examine further these phenomenon at an individual-level, as well as to explore circadian and affective interactions at a couple-level for perhaps the first time by monitoring mood, interpersonal interactions, sleep, activity, and light in 31 bed-sharing cohabitating couples over the course of 7 days. Participants’ depression, well-being, relationship satisfaction, and morningness-eveningness were also assessed. Systematic daily patterning was found in all three measures of affect, and was moderated by depression, well-being, and morningness-eveningness. Within-couple affective synchrony (covariation) was positively associated with relationship satisfaction, within-couple morningness- eveningness similarity, and synchrony of sleep timing. Finally, day-to-day within-couple sleep timing synchrony predicted the tenor of the following day’s partner interactions and affect. These data provide further evidence of potentially important interactions between sleep, circadian, affective processes both within- and between-individuals.